La³⁺-Catalyzed Methanolysis of Hydroxypropyl-p-nitrophenyl Phosphate as a Model for the RNA Transesterification Reaction

Abstract

The methanolysis of hydroxypropyl-p-nitrophenyl phosphate (HPNPP, 1) promoted by La(OTf)(3) under buffered conditions was studied in methanol as a function of pH at 25 degrees C. (31)P NMR studies at -90 degrees C indicate that there are at least three La/1 complexes formed at pH approximately 5.3 of 1:1, 2:2, and 1:2 stoichiometry. Kinetic studies of the observed pseudo-first-order rate constants for the methanolysis of 1 as a function of [La(3+)] at 4.5 < pH < 10.5 indicate there are two general pH regimes. In the low pH regime between 4.5 and 7.6, the plots of k(obs) versus [La(3+)] exhibit saturation behavior with very strong 1:1 binding, with a plateau rate constant that depends on [OCH(3)(-)]. The catalytically productive species is shown to be a 2:2 complex of La(3+) and 1, where the phosphate is proposed to be doubly activated, thereby promoting the methoxide reaction by some 4.6 x 10(10)-fold. In the high pH regime from 7.9 to 10.5, 1:1, 2:2, and 2:1 La(3+)/1 complexes are formed with the La(3+) coordinated in the form of [La(3+)(OCH(3)(-))](1,2). Throughout this pH regime at high [La(3+)], a saturation complex, (La(3+)OCH(3)(-))(2)/1, is formed that spontaneously decomposes with a rate constant of (5-10) x 10(-)(3) s(-)(1), leading to an acceleration of 10(9)-fold at pH 8.0.

Altered Transition State for the Reaction of an RNA Model Catalyzed by a Dinuclear Zinc(II) Catalyst

“…Natural abundance and bridge-labeled isotopic isomers of HpPNP were made using a slight adaptation of a previously published procedure5 which was in turn adapted from the original synthetic procedure 2. The procedure used is illustrated in the following example: 11 mL of propylene oxide (157 mmol) and 360 mg (0.828 mmol) of the di-cyclohexylammonium salt of p -nitrophenyl phosphate ( p -NPP) were stirred vigorously at 30°C in 10 mL of water in a capped round bottom flask.…”

Bio-inspired approaches to accelerating metal ion-promoted reactions: enzyme-like rates for metal ion mediated phosphoryl and acyl transfer processes

“…OMe for this process is 2.6 × 10 −3 dm 3 mol −1 s −1 at 25 °C [29,30]. A subsequent study of the kinetics of the cyclization of 6a-g promoted by the dinuclear Zn(II) complex 8 revealed that the general mechanism involves saturation binding of the substrate to the complex followed by unimolecular decomposition of a 8:6 complex to give the corresponding phenoxide products and the cyclic ester 7 [31] as in eq.…”

Properties of surface-cross-linked micelles probed by fluorescence spectroscopy and their catalysis of phosphate ester hydrolysis

“…HPNPP was prepared according to a literature procedure [19]. A stock solution (10 mM) of HPNPP in Millipore water was prepared.…”